title: Characterization of PUD-1 and PUD-2, two proteins up-regulated in a long-lived daf-2 mutant.
abstract: C. elegans PUD-1 and PUD-2, two proteins up-regulated in daf-2(loss-of-function) (PUD), are homologous 17-kD proteins with a large abundance increase in long-lived daf-2 mutant animals of reduced insulin signaling. In this study, we show that both PUD-1 and PUD-2 are abundantly expressed in the intestine and hypodermis, and form a heterodimer. We have solved their crystal structure to 1.9-Å resolution and found that both proteins adopt similar β-sandwich folds in the V-shaped dimer. In contrast, their homologs PUD-3, PUD-4, PUDL-1 and PUDL-2 are all monomeric proteins with distinct expression patterns in C. elegans. Thus, the PUD-1/PUD-2 heterodimer probably has a function distinct from their family members. Neither overexpression nor deletion of pud-1 and pud-2 affected the lifespan of WT or daf-2 mutant animals, suggesting that their induction in daf-2 worms does not contribute to longevity. Curiously, deletion of pud-1 and pud-2 was associated with a protective effect against paralysis induced by the amyloid β-peptide (1-42), which further enhanced the protection conferred by daf-2(RNAi) against Aβ.
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Yue-He
authors.initials: YH
authors.lastname: Ding
authors.forename: Yun-Guang
authors.initials: YG
authors.lastname: Du
authors.forename: Shukun
authors.initials: S
authors.lastname: Luo
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Li
authors.forename: Tie-Mei
authors.initials: TM
authors.lastname: Li
authors.forename: Sawako
authors.initials: S
authors.lastname: Yoshina
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.forename: Karsten
authors.initials: K
authors.lastname: Klage
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.forename: Keqiong
authors.initials: K
authors.lastname: Ye
authors.forename: Meng-Qiu
authors.initials: MQ
authors.lastname: Dong
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D051858:Forkhead Transcription Factors; D015870:Gene Expression; D057927:Hydrophobic and Hydrophilic Interactions; D008136:Longevity; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011972:Receptor, Insulin / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D010446:Peptide Fragments; D014157:Transcription Factors; C075222:amyloid beta-protein (1-42); C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin